Melanin is dark brown pigments found in the eyes or on the skin, hair, etc. and plays positive roles in protecting the body or maintaining the body temperature, through blocking the penetration of ultraviolet radiation in a way that absorbs the ultraviolet radiation over a certain amount. However, excessive exposure to ultraviolet radiation leads to overexpression of melanin for blocking the skin penetration thereof, which often causes skin color changes. It is known that melanin is produced by the concurrence of melanin-producing enzymes (e.g., tyrosinase) and hormones.
Melanoma is a tumor formed by malignant alteration of melanin-producing cells (i.e., melanocytes). Although melanoma can occur in any body parts where melanocytes are present, the incidence thereof is the highest in the skin. And also, it is known that its malignancy is significantly high among various skin tumors. Although the incidence of melanoma is relatively low in the East in comparison with in the West, it is increasing year by year, showing the tendency that it begins to increase from twenty-year-old; and then rapidly increases in more than forty-year-old. It is thought that melanoma results mainly from genetic causes and/or exposure to ultraviolet radiation.
Meanwhile, microphthalmia-associated transcription factor (MITF) is one of the transcription factors which control the melanin production in melanocytes. When the skin is stimulated by ultraviolet radiation, α-melanocyte stimulating hormone (α-MSH) is secreted in the keratinocytes and then coupled with melanocortin-1 receptor (MC1-R) on the surface of melanocytes. As a result thereof, the concentration of cAMP in the melanocytes is increased and the expression of MITF is increased through multiple pathways. MITF subsequently induces the expressions of melanin-production enzymes, i.e., tyrosinase, TRP1, and TRP2, which results in increasing the production of melanin. Tyrosinase produces L-dopaquinone by hydroxylation and oxidation of tyrosine. The resulting L-dopaquinone depletes cysteine, thereby forming eumelanine. Human skin is known to be affected most significantly by the amount of eumelanin, suggesting that MITF is a critical factor of skin pigmentation (Gillbro J M and Olsson M J. 2011. The melanogenesis and mechanism of skin-lightening agents-existing and new approaches. Int J Cos. Sci. 33:210).